The objective of this project is to specifically develop a yeast-based immunotherapeutic (Tarmogen(r) product) for the prevention and treatment of human Mycobacterium tuberculosis infection. This application involves a collaborative effort between GlobeImmune, Inc., a Colorado biotechnology company (GlobeImmune), and Colorado State University (CSU). GlobeImmune will be heading this initiative to combine CSU's expertise in tuberculosis (TB) with GlobeImmune's expertise in the preclinical and clinical development of a unique vaccine approach known as Tarmogen(r) technology. This team of academics and biotechnologists provides innovative solutions to five areas that have been problematic in the development of a vaccine approach for treating TB, namely: (1) Use of a vaccine platform that specifically targets the T cell pathway(s) relevant for use against TB; (2) Selection of an animal model for preclinical testing that will be more predictive of clinical utility; (3) Ability to test vaccine candidates against newly emerging, highly virulent, multi-drug resistant, clinical strains of M. tuberculosis; (4) Choice of target antigens with the potential for greater clinical utility; nd (5) Ability to manufacture vaccine rapidly at large scale and with excellent stability. The approach involves the development and use of recombinant yeast expressing one or more TB antigens, including new antigen targets developed by CSU. The resulting TB-specific Tarmogen(r) products will be tested and validated using established mouse modeling in vivo and in vitro to document TB antigen specific immune responses, followed by testing in prophylactic mouse and guinea pig challenge models. These data will be used to further test the most promising TB Tarmogen products in a therapeutic guinea pig model that is highly relevant to TB in humans, including testing the immunotherapy candidates against newly emerging, highly virulent, multi-drug resistant strains of TB. The overall goal of the project will be to complete preclinical testing of one or more immunotherapeutic compositions for the pre and post-exposure prevention of TB as well as treatment of TB in order to advance the composition(s) into human clinical trials.